When
cocaine arrives at the brain reward system, it blocks
the dopamine transport sites, which are responsible for
the reuptake of dopamine in dopaminergic synapeses in
this region. Therefore, dopamine is not removed from the
synaptic gap, and it remains free there, in ever increasing
amounts, because successive nervous stimuli continue to
arrive and to release dopamine. The effect remains until
cocaine is removed from the presynaptic terminals. It
is believed that the abnormally long presence of dopamine
in the brain is responsible for the pleasure effects associated
to the use of cocaine. The prolonged use of cocaine makes
the brain to adapt to it, and the overall synthesis of
dopamine by the neurons is decreased. Between cocaine
doses, or when the use of cocaine is interrupted, the
drug user experiences the opposite of pleasure, due to
the low levels of dopamine: fatigue, depression and altered
moods.